Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) and accounts for approximately one-quarter of NHL cases. Patients typically present with enlarged lymph nodes in the neck or abdomen. DLBCL’s first-line immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin and prednisone) curing approximately two-thirds of patients. The prognosis is poor for DLBCL patients who receive first-line chemoimmunotherapy but develop early relapse or refractoriness. Treatment options for refractory patients include salvage chemoimmunotherapy, monoclonal antibodies, CAR-T or autologous stem cell transplantation. We will present a case of primary refractory DLBCL.

A 57-year-old male patient with no chronic illness presented to the internal medicine outpatient clinic complaining of abdominal pain and was referred to us due to the detection of conglomerate lymphadenopathy (LAP) in the abdomen on imaging. Positron Emission Tomography (PET-CT) revealed multiple LAP’s within the abdomen, the largest measuring 80 mm in diameter and with an SUV(max) value of 21.8. A tru-cut biopsy was performed from the large intra-abdominal LAP. The results were DLBCL with Bcl-2 (+), Bcl-6 (+), and Ki-67 85-90%. Myc could not be tested for technical reasons. No infiltration was detected in the bone marrow biopsy. The patient received 3 cycles of R-CHOP chemotherapy protocol, and a PET-CT scan was performed for interim evaluation. The PET-CT scan showed persistent conglomerate LAP’s with an SUV(max) value of 27.02 and a maximum diameter of 58 mm. The patient, considered refractory, received two cycles of R-DHAP (Rituximab-Dexamethasone, Cytarabine Cisplatin) chemotherapy protocol and a PET-CT scan was performed for response evaluation. The PET-CT scan showed multiple LAPs, the largest of which was 83 mm in diameter and had an SUV(max) of 31.45. A tru-cut biopsy was performed again from the largest intra-abdominal lymph node for confirmation of the diagnosis. Pathology was similar to the previous biopsy and c-myc was weak (+) (10-15%). The patient received two cycles of the R-GemOX (rituximab, gemcitabine, oxaliplatin) protocol. Only abdominal CT was scanned and no reduction in the mass was observed. Glofitamab therapy was initiated with off-label consent. The first and second cycle was completed. The patient did not develop cytokine release syndrome or neuropathy. A PET-CT scan was scheduled for 3 weeks later for response evaluation. The PET-CT scan showed that the intra-abdominal mass had regressed to 8 mm and the SUV(max) value to 3.44. The patient, who responded to glofitamab treatment, was offered autologous stem cell transplantation or CAR-T (Chimeric Antigen Receptor T-cell) therapy options. The patient requested to be referred to a center where CAR-T therapy could be performed. The patient is currently awaiting CAR-T therapy.

In eligible DLBCL patients, salvage chemoimmunotherapy and/or monoclonal antibodies can be used as bridge therapies to OKIT or CAR-T therapies. Glofitamab is a bispecific antibody targeting CD20 and CD3, approved for r/r DLBCL patients after at least two prior lines of therapy. In a study, Glofitamab demonstrated a 46% ORR (27% CR; 19% PR) and manageable safety in heavily pretreated r/r DLBCL patients.